REGULATION OF T CELL RECEPTOR GENE DIFFERENTIATION

描述：(改编自申请人的摘要)所有已知的脊椎动物 有三组淋巴细胞，B细胞，α/β(Ab)T细胞，以及 由其各自的抗原受体定义的伽马/德尔塔(Gd)T细胞。 Gd T细胞在宿主保护和维持中的作用很差 许多旨在解决这一问题的研究已经比较了 将gdT细胞与其他两种类型的淋巴细胞进行对比。 有趣的是，gd T细胞新出现的功能特性表明 它们可能有迄今为止被认为是B细胞特异的或抗体的特征 T细胞特异性。 在本申请中，描述的研究将继续我们的 GDT细胞发育检查。新出现的信息再次表明， 一些gd T细胞与ab T细胞高度相似，来源于 相同的血统，而其他人类似B细胞，甚至在胸腺外 派生的。申请列出了七个具体目标，成功实现了 可以证实gd T细胞发育的这种“双途径”观点，并提供 对如何监管发展的重要机械性洞察。是这样的 知识可以显著改善我们对T细胞的基本描述 发展。此外，它还提供了关于T细胞如何发展的指导 可能在自身免疫的情况下被实验操纵， 免疫缺陷，或移植。

DESCRIPTION: (Adapted from the applicant's abstract) All known vertebrates harbor three sets of lymphocytes, B cells, alpha/beta (ab) T cells, and gamma/delta (gd) T cells, defined by their respective antigen receptors. The role of gd T-cells in host protection and maintenance is poorly understood, and many studies aimed at resolving this have compared and contrasted gd T cells with the other two types of lymphocytes. Interestingly, emerging functional properties of gd T-cells suggest that they may share features hitherto regarded as B-cell-specific or ab T-cell-specific. In this application, studies are described that will continue our examination of gd T-cell development. Again, emerging information indicates that some gd T cells are highly similar to ab T cells, being derived from the same lineage, whereas others are B-cell like, even being extrathymically derived. The application lists seven specific aims, the success of which can confirm this "dual pathway" view of gd T-cell development and provide important mechanistic insight into how development is regulated. Such knowledge can significantly improve our basic depiction of T-cell development. In addition, it provides guidance as to how T-cell development might be experimentally manipulated in cases of autoimmunity, immunodeficiency, or transplant.